Conjugated vaccines rely on antigen attachment to a carrier protein or vector, allowing an otherwise non-immunogenic antigen to take on the immunogenicity of the carrier. Conjugated vaccines employing the widely-used tetanus toxoid carrier have been shown to have reduced efficacy in individuals previously exposed to tetanus toxoid, as pre-existing immunity against the carrier neutralizes the conjugated vaccine. Schutze et al., Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. J. Immunol. 1985; 135(4):2319-22. Other common carriers, such as adenovirus, are also likely to be neutralized by pre-existing immunity, especially upon repeated vaccinations or booster injections. Pinto et al., Induction of CD8+ T cells to an HIV-1 antigen through a prime boost regimen with heterologous E1-deleted adenoviral vaccine carriers. J. Immunol. 2003p; 171(12):6774-9.
Methods are provided herein for improving a specific immune response in a subject to a target antigen having low predicted linear B-cell epitope scoring, the method comprising administering to the subject a polypeptide conjugate comprising the target antigen covalently attached to a carrier polypeptide by means of an intervening linker polypeptide, wherein the linker polypeptide and/or the carrier polypeptide exhibit higher predicted linear B-cell epitope scoring than the target antigen, and wherein the carrier polypeptide does not stimulate a substantial T-cell response.